This project represents an on-going study of the mechanical, metabolic and electrical abnormalities of the diseased heart. It is concerned primarily with the identification of the mechanical abnormalities which presage myocardial failure and with mechanisms of fetal tachyarrhythmias in experimental ischemic heart disease. Proposed work will be in three general areas. One of these involves a prospective study of the diastolic properties and dimensional analysis of the left ventricle in patients with chronic volume overload utilizing non-invasive (echography) and invasive technics. It is aimed at identifying early plastic changes of the ventricle and associated abnormalities of systolic performance which may be helpful in choosing the optimal time for surgical intervention in patients with chronic volume overload. A related project will examine the relationships between ventricular wall thickness, vascular volumes, ventricular compliance and function in the intact dog heart. The second study is concerned with mechanisms of ventricular tachyarrhythmias in experimental myocardial ischemia and abrupt reperfusion. Using computerized technics for recording strength-interval curves and conduction, the time course and dispersion of recovery properties will be examined during acute myocardial ischemia and abrupt reperfusion with particular attention given to the form and depth of phase 3 dips of anodal strength-interval curves and their possible role in the genesis of reperfusion arrhythmias. Lastly, a study will be made of the effects of diastolic pressure augmentation (external counterpulsation) and vasodilator therapy (nitroglycerine) in patients with acute myocardial infarction. The aim of this project is to examine methods for reducing infarct size and its mechanical and electrical consequences. BIBLIOGRAPHIC REFERENCES: Apstein, C. S., Bing, O. H. L. and Levine, H. J. Cardiac Muscle Function during and after Hypoxia: effects of glucose concentration, mannitol and isoproterenol. J. Mol. and Cell. Cardiol. 8:627-640, 1976. Naimi, S., Avitall, B., Mieszala, J. and Levine, H. J. Dispersion of effective refractory period during abrupt reperfusion of ischemic myocardium in dogs. Am. J. of Cardiol. 39:407-412, 1977.